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    Summary
    EudraCT Number:2012-002473-61
    Sponsor's Protocol Code Number:GS-US-321-0102
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-04-08
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedDenmark - DHMA
    A.2EudraCT number2012-002473-61
    A.3Full title of the trial
    A Phase 2b, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of GS-6624, a Monoclonal Antibody Against Lysyl Oxidase Like 2 (LOXL2) in Subjects with Primary Sclerosing Cholangitis (PSC)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An investigational study to assess the safety and efficacy of a new investigational drug in subjects with primary sclerosing cholangitis (PSC)
    A.4.1Sponsor's protocol code numberGS-US-321-0102
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGilead Sciences Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGilead Sciences Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGilead Sciences Inc
    B.5.2Functional name of contact pointMedical Monitor
    B.5.3 Address:
    B.5.3.1Street Address333 Lakeside Drive
    B.5.3.2Town/ cityFoster City
    B.5.3.3Post codeCA 94404
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1650574 3000
    B.5.5Fax number+1650578 9264
    B.5.6E-mailclinical.trials@gilead.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code GS-6624
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGS-6624
    D.3.9.2Current sponsor codeGS-6624
    D.3.9.4EV Substance CodeSUB33243
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGS-6624
    D.3.9.2Current sponsor codeGS-6624
    D.3.9.4EV Substance CodeSUB33243
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary Sclerosing Cholangitis (PSC)
    E.1.1.1Medical condition in easily understood language
    Primary Sclerosing Cholangitis (PSC)
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10036732
    E.1.2Term Primary sclerosing cholangitis
    E.1.2System Organ Class 100000004871
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate whether GS-6624 is effective at preventing the progression of liver fibrosis in subjects with PSC.
    E.2.2Secondary objectives of the trial
    • To assess the safety of GS-6624 in subjects with PSC;
    • To assess the pharmacokinetics of GS-6624 in subjects with PSC;
    • To assess the immunogenicity of GS-6624 in this population;
    • To assess whether baseline serum LOXL2 levels are predictive of response to GS-6624 therapy (active groups) and/or prognostic for disease progression (placebo group);
    • To compare different efficacy assessment tools in this population;
    • To determine whether non-invasive measures of fibrosis can predict regression of fibrosis and reversal of cirrhosis in this population.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    MRE Substudy
    The Magnetic Resonance Elastography (MRE) Substudy will consist of approximately 50 subjects from selected investigative sites with the ability to perform MRE. Subjects will undergo a liver stiffness assessment by MRE at Baseline Visit, Week 48 and the End of Treatment Visit (Week 96).

    Impedance Ultrasonography Substudy
    The Impedance Ultrasonography Substudy will consist of approximately 50 subjects from selected investigative sites with the ability to perform impedance ultrasonography (such as Fibroscan). Subjects will undergo a liver stiffness assessment by impedance ultrasonography at Baseline Visit, Week 48 and the End of Treatment Visit (Week 96).
    E.3Principal inclusion criteria
    1. Males and females 18 - 70 years of age;
    2. Willing and able to provide informed, written consent;
    3. Chronic cholestatic liver disease of at least 6 months’ duration;
    4. Liver biopsy consistent with PSC; If a liver biopsy has been performed
    within 3 months of the Screening Visit, tissue from that biopsy may be
    used as the screening biopsy. Slides would be re-cut from the existing
    tissue block and submitted for central reader assessment. Some subjects
    with PSC may have a normal liver biopsy, in the event of a normal liver
    biopsy, the subject must have an abnormal MRCP
    5. MRCP consistent with PSC; Some subjects with PSC may have a
    normal MRCP, in the event of a normal MRCP, the subject must have an
    abnormal liver biopsy;
    6. Exclusion of other causes of liver disease including viral hepatitis, alcoholic liver disease, primary biliary cirrhosis and secondary sclerosing cholangitis;
    7. Must be willing and able to comply with all study requirements;
    8. Must have AST and ALT ≤ 10 x clULN;
    9. Must have serum creatinine < 2.0 mg/dL (176.8umol/L);
    10. Female subjects of childbearing potential must have a negative serum pregnancy test prior to starting study treatment. For the purposes of this study, a female subject of childbearing
    potential is a woman who has not had a hysterectomy, bilateral oophorectomy, or medically-documented ovarian failure. Women ≤ 50 years of age with amenorrhea of any duration
    will be considered to be of childbearing potential;
    11. All sexually active female subjects who are of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse from the Screening Visit throughout the study period and for 90 days following the last dose of study drug. If females utilize
    hormonal agents as one of their contraceptive methods, the same hormonal method must have been used for at least 1 month before study dosing. Females on hormonal methods must utilize a barrier method as the other form of contraception;
    12. Lactating females must agree to discontinue nursing before study
    investigational medicinal product administration;
    13. Male subjects, if not vasectomized, are required to use barrier
    contraception (condom plus spermicide) during intercourse from
    screening through to study completion and
    for 90 days from the last dose of study investigational medicinal product.
    E.4Principal exclusion criteria
    1. Pregnant or breast feeding;
    2. Any evidence of hepatic decompensation past or present, including ascites, episodes of hepatic encephalopathy, variceal bleeding or a prolonged PT/INR;
    3. HCV RNA positive;
    4. HBsAg positive;
    5. Positive anti-mitochondrial antibody;
    6. Alcohol consumption greater than 21 oz/week for males or 14
    oz/week for females;
    7. Moderately active UC defined as either a partial Mayo score of > 4,
    bleeding score of >1, or current use of oral corticosteroid therapy
    and/or any inhibitor of TNF-α or α4β7 integrin antagonist
    8. Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at Screening. Subjects on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening may be included in the study. Subjects with a positive urine drug screen due to
    prescription opiod-based medications are eligible if the prescription and diagnosis are reviewed and approved by the investigator.
    9. Clinically significant cardiac disease;
    10. History of cholangiocarcinoma. If a dominant stricture is found, cholangiocarcinoma must be ruled out by brush cytology or biopsy prior to randomization;
    11. History of other cancers, other than non-melanomatous skin cancer, within 5 years prior to screening;
    12. Ascending cholangitis within 60 days of screening;
    13. Presence of a percutaneous drain or bile duct stent;
    14. Major surgical procedure within 30 days prior to screening or the presence of an open wound;
    15. Known hypersensitivity to the investigational product or any
    of its formulation excipients;
    16. History of bleeding diathesis within 6 months of screening;
    17. Unavailable for follow-up assessment or concern for subject’s compliance with the protocol procedures;
    18. Participation in a clinical trial of an investigational drug or device within 30 days prior to screening;
    19. Any other condition that in the opinion of the investigator renders the subject a poor risk for inclusion into the study
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint will be:
    Change from baseline in morphometric quantitative collagen on liver biopsy at Week 96.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Subjects will complete the 96 week treatment course with blinded study medication and will undergo liver biopsy at Week 96
    E.5.2Secondary end point(s)
    Exploratory efficacy endpoints will include:
    • Change from baseline in morphometric quantitative collagen on liver biopsy at Week 48;
    • Change from Baseline in the Mayo risk score at 4 week intervals;
    • Change from Baseline in the MELD score at 4 week intervals;
    • Assess the rate of events related to progression of PSC in each treatment arm, including variceal bleeding, ascites, encephalopathy, ascending cholangitis, cholangiocarcinoma, hepatocellular carcinoma, transplant and death.
    • Change from Baseline in serum alkaline phosphatase levels at 4 week intervals;
    • Change from Baseline in the Ishak fibrosis stage on liver biopsy at weeks 48 and 96;
    • Change from Baseline in α-smooth muscle actin on liver
    biopsy at weeks 48 and 96;
    • Change from Baseline on a VAS assessment of pruritus severity at weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96;
    • Change from baseline in serum LOXL2 levels at weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96;
    • Change from baseline in ELF™ test at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96;
    • Change from baseline in FibroSURE/FibroTest/FibroMAX at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96;
    • MRCP as compared to Baseline at weeks 48 and 96;
    • For a subset of approximately 50 subjects, change from baseline in liver stiffness as measured by MRE at weeks 48 and 96;
    • For a subset of approximately 50 subjects, change from baseline in liver stiffness as measured by impedance ultrasonography at weeks 48 and 96.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary Endpoints:
    Subjects will complete the 96 week treatment course with blinded study medication and will undergo repeat liver biopsy at week 96. Other endpoints will be assessed at weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96 as detailed in each specific endpoint

    • For a subset of approximately 50 subjects, change from baseline in liver stiffness as measured by MRE at weeks 48 and 96;
    • For a subset of approximately 50 subjects, change from baseline in liver stiffness as measured by impedance ultrasonography at weeks 48 and 96.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last Subject Last visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months11
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 225
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 95
    F.4.2.2In the whole clinical trial 225
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Gilead will provide no post trial treatment. Treatment following the trial will not be be the standard offered to someone with their underlying disease and will be determined by the treating physician.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-04-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-05-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-08-24
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